ZIF-8 with encapsulated dihydroartemisinin in a drug delivery system for protection against Plasmodium berghei ANKA-induced experimental cerebral malaria in C57BL/6N mice
ABSTRACT Cerebral malaria (CM), primarily caused by Plasmodium falciparum, is the primary cause of malaria-related fatalities. CM treatment faces significant challenges due to limited therapeutic options and the emergence of antimalarial drug resistance. Dihydroartemisinin (DHA) is the first-line th...
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American Society for Microbiology
2025-07-01
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| Series: | Microbiology Spectrum |
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| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.02366-24 |
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| author | Yuting Li Liu-Gen Li Huiyin Zhu Daiqian Zhu Haimei Shi Wei Wang Jinyu Mo Jianhai Yin Tong-fei Li Jian Li |
| author_facet | Yuting Li Liu-Gen Li Huiyin Zhu Daiqian Zhu Haimei Shi Wei Wang Jinyu Mo Jianhai Yin Tong-fei Li Jian Li |
| author_sort | Yuting Li |
| collection | DOAJ |
| description | ABSTRACT Cerebral malaria (CM), primarily caused by Plasmodium falciparum, is the primary cause of malaria-related fatalities. CM treatment faces significant challenges due to limited therapeutic options and the emergence of antimalarial drug resistance. Dihydroartemisinin (DHA) is the first-line therapeutic agent for malaria. However, it encounters limitations such as poor solubility, inadequate selectivity, and rapid elimination. Here, we introduced a facile and effective approach using zeolite imidazolium framework-8 (ZIF-8) encapsulated with DHA (DHA@ZIF-8) and assessed its therapeutic efficacy in an experimental cerebral malaria model. The DHA@ZIF-8 demonstrated excellent drug-loading capacity, high stability, prolonged drug release, and improved targeted elimination of Plasmodium parasites within infected red blood cells (iRBCs). This minimized damage to brain microvascular endothelial cells (BMECs) and protected organs from injury, increasing the survival time of the infected mice. Compared to free DHA, DHA@ZIF-8 exhibited better antimalarial efficacy and almost no side effects. This study highlights ZIF-8’s potential as a reliable, stable, and efficient drug delivery vector for DHA to improve CM therapy.IMPORTANCEFor the treatment of human malaria, artemisinin-based drugs remain the first-line treatment option. However, their utility is constrained by their short half-life in vivo. Consequently, extending the duration for drug efficacy in the body is a critical issue that needs to be addressed. Metal-organic frameworks are a promising choice for drug loading. In the present study, DHA@ZIF-8 and DHA@MOF were constructed and characterized and were assessed in an experimental cerebral malaria model of C57BL/6 N mice induced by Plasmodium berghei ANKA strain. Data show that DHA@ZIF-8 has a worthy therapeutic effect on experimental cerebral malaria. It will offer a new option for human cerebral malaria (HCM) treatment. |
| format | Article |
| id | doaj-art-a48dd1c3ffc9443aabf1746c6e610a2a |
| institution | OA Journals |
| issn | 2165-0497 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj-art-a48dd1c3ffc9443aabf1746c6e610a2a2025-08-20T02:38:10ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972025-07-0113710.1128/spectrum.02366-24ZIF-8 with encapsulated dihydroartemisinin in a drug delivery system for protection against Plasmodium berghei ANKA-induced experimental cerebral malaria in C57BL/6N miceYuting Li0Liu-Gen Li1Huiyin Zhu2Daiqian Zhu3Haimei Shi4Wei Wang5Jinyu Mo6Jianhai Yin7Tong-fei Li8Jian Li9School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei, ChinaSchool of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei, ChinaSchool of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei, ChinaSchool of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei, ChinaSchool of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei, ChinaKey Laboratory of National Health Commission on Parasitic Disease Prevention and Control, Jiangsu Provincial Key Laboratory on Parasites and Vector Control Technology, Jiangsu Institute of Parasitic Diseases, Wuxi, Jiangsu, ChinaSchool of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei, ChinaNational Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), NHC Key Laboratory of Parasite and Vector Biology, WHO Collaborating Centre for Tropical Diseases, National Center for International Research on Tropical Diseases, Shanghai, ChinaSchool of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei, ChinaSchool of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei, ChinaABSTRACT Cerebral malaria (CM), primarily caused by Plasmodium falciparum, is the primary cause of malaria-related fatalities. CM treatment faces significant challenges due to limited therapeutic options and the emergence of antimalarial drug resistance. Dihydroartemisinin (DHA) is the first-line therapeutic agent for malaria. However, it encounters limitations such as poor solubility, inadequate selectivity, and rapid elimination. Here, we introduced a facile and effective approach using zeolite imidazolium framework-8 (ZIF-8) encapsulated with DHA (DHA@ZIF-8) and assessed its therapeutic efficacy in an experimental cerebral malaria model. The DHA@ZIF-8 demonstrated excellent drug-loading capacity, high stability, prolonged drug release, and improved targeted elimination of Plasmodium parasites within infected red blood cells (iRBCs). This minimized damage to brain microvascular endothelial cells (BMECs) and protected organs from injury, increasing the survival time of the infected mice. Compared to free DHA, DHA@ZIF-8 exhibited better antimalarial efficacy and almost no side effects. This study highlights ZIF-8’s potential as a reliable, stable, and efficient drug delivery vector for DHA to improve CM therapy.IMPORTANCEFor the treatment of human malaria, artemisinin-based drugs remain the first-line treatment option. However, their utility is constrained by their short half-life in vivo. Consequently, extending the duration for drug efficacy in the body is a critical issue that needs to be addressed. Metal-organic frameworks are a promising choice for drug loading. In the present study, DHA@ZIF-8 and DHA@MOF were constructed and characterized and were assessed in an experimental cerebral malaria model of C57BL/6 N mice induced by Plasmodium berghei ANKA strain. Data show that DHA@ZIF-8 has a worthy therapeutic effect on experimental cerebral malaria. It will offer a new option for human cerebral malaria (HCM) treatment.https://journals.asm.org/doi/10.1128/spectrum.02366-24cerebral malariadihydroartemisininnanodrugdrug deliveryzeolitic imidazolate framework-8 |
| spellingShingle | Yuting Li Liu-Gen Li Huiyin Zhu Daiqian Zhu Haimei Shi Wei Wang Jinyu Mo Jianhai Yin Tong-fei Li Jian Li ZIF-8 with encapsulated dihydroartemisinin in a drug delivery system for protection against Plasmodium berghei ANKA-induced experimental cerebral malaria in C57BL/6N mice Microbiology Spectrum cerebral malaria dihydroartemisinin nanodrug drug delivery zeolitic imidazolate framework-8 |
| title | ZIF-8 with encapsulated dihydroartemisinin in a drug delivery system for protection against Plasmodium berghei ANKA-induced experimental cerebral malaria in C57BL/6N mice |
| title_full | ZIF-8 with encapsulated dihydroartemisinin in a drug delivery system for protection against Plasmodium berghei ANKA-induced experimental cerebral malaria in C57BL/6N mice |
| title_fullStr | ZIF-8 with encapsulated dihydroartemisinin in a drug delivery system for protection against Plasmodium berghei ANKA-induced experimental cerebral malaria in C57BL/6N mice |
| title_full_unstemmed | ZIF-8 with encapsulated dihydroartemisinin in a drug delivery system for protection against Plasmodium berghei ANKA-induced experimental cerebral malaria in C57BL/6N mice |
| title_short | ZIF-8 with encapsulated dihydroartemisinin in a drug delivery system for protection against Plasmodium berghei ANKA-induced experimental cerebral malaria in C57BL/6N mice |
| title_sort | zif 8 with encapsulated dihydroartemisinin in a drug delivery system for protection against plasmodium berghei anka induced experimental cerebral malaria in c57bl 6n mice |
| topic | cerebral malaria dihydroartemisinin nanodrug drug delivery zeolitic imidazolate framework-8 |
| url | https://journals.asm.org/doi/10.1128/spectrum.02366-24 |
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